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PLOS Papers on Anticancer Drugs, SARS-CoV-2 Diversity in Hosts, Ovarian Cancer Blood Transcripts

In PLOS Genetics, researchers from the North Carolina State University, the National Institute of Environmental Health Sciences, and elsewhere present findings from a screen for genes influencing response to dozens of approved cancer drugs. With a high-throughput screening and genome-wide association study that included 44 anticancer compounds and some 680 genotyped lymphoblastoid cell lines generated for the 1000 Genomes Project, the team identified genes with suspected links to drug response, using expression and functional analyses to focus in on an enzyme-coding gene called NQO1 that was linked to dose-response features for several different drugs. "Baseline gene expression of NQO1 was positively correlated with response for 43 of the 44 treatments surveyed," the authors write, adding that the gene "has potential use as a therapeutic target, for example, suppressing NQO1 expression to increase sensitivity to particular drugs."

A University of Wisconsin at Madison- and Fred Hutchinson Cancer Research Center-led team tracks SARS-CoV-2 transmission in relation to diversity in individual hosts for a paper in PLOS Pathogens. By digging into deep genome sequence data for 133 SARS-CoV-2 isolates from individuals with acute COVID-19 infections, the investigators identified intra-host single-nucleotide variants (iSNVs) and variants that distinguished viruses from one host and the next, bringing in household infection and other epidemiological clues, experimental data, and bioinformatics to look at the transmission of iSNVs. "We find that within-host diversity is low and transmission bottlenecks are narrow, with very few viruses founding most infections," they report. "Within-host variants are rarely transmitted, even among individuals within the same household, and are rarely detected along phylogenetically linked infections in the broader community. These findings suggest that most variation generated within-host is lost during transmission."

Investigators in Norway search for blood transcripts that may predict impending ovarian cancer diagnoses. As they report in PLOS One, the researchers relied on blood samples collected for the Norwegian Women and Cancer population study, comparing array-based blood gene expression profiles for dozens of women who did or did not develop epithelial ovarian cancer (EOC). Along with potential blood transcriptome differences between ovarian cancer cases and controls, the team considered samples from individuals with specific ovarian cancer subtypes or metastatic disease. "This nested case-control study of gene expression in whole blood collected up to 7 years prior to EOC diagnosis revealed no statistically significant global or gene-wise associations with EOC status," the authors report, though they added that four genes had nominal associations with metastatic forms of the disease in a targeted analysis of 42 genes previously implicated in EOC.

The Scan

Steps for Quick Review

The US Food and Drug Administration is preparing for the quick review of drugs and vaccines for the Omicron variant, according to the Wall Street Journal.

Moving Away From Using Term 'Race'

A new analysis finds that geneticists are using the term "race" in their papers less than in years past, as Science reports.

Point of the Program

The Guardian writes that some scientists have called the design of a UK newborn sequencing program into question.

Science Papers Present Multi-Omic Analysis of Lung Cells, Regulation of Cardiomyocyte Proliferation

In Science this week: a multi-omic analysis of lung cells focuses on RIT1-regulated pathways, and more.